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So Who Really Needs Infertility Surgery?

Today we will talk about trying to figure out who needs infertility surgery and who does not. Some cases are obvious, and some are very borderline.

This blog will discuss the case of the fibroid uterus, another blog will follow concerning other problems.

I’ll start with a little story. Cathy was a 40-year-old woman who had been trying to become pregnant for years. Before I examined her she said that doctors have told her she has a fibroid, but she did not think it was causing her any problems.

When I got to her exam, I found a huge fibroid growing all the way to her navel. On ultrasound she had a fibroid larger than a grapefruit distorting her entire uterus making it impossible to become pregnant. In addition, she was anemic because the fibroid was causing her to have super heavy periods. Upon further questioning, she revealed that she had been told about this problem years ago, but figured she would just try on her own just in case.

So here is a woman who absolutely needed surgery to become pregnant, and for some reason did not want get it done. I gently explained her that she could not get pregnant without an operation, and she told me she was really going to consider it this time, but never returned.

I can’t explain her behavior; maybe fear, or maybe a family member was giving her advice. But the point here is that from my end, this was easy advice to give, it was clear, she needed surgery. Very few cases are as clear as this. In fact in most cases of infertility surgery, non-surgery is a real option.
Lets go through a few more scenarios.Here is another easy fibroid case, the case of the submucus myoma (myoma=fibroid). Submucus means right in the cavity itself, it grows among the glands that are necessary to hold an embryo.
A submucus myoma even as small as a half of an inch can be a problem because it can disrupt the uterine lining (the endometrium), interfering with implantation. Plus they can cause heavy bleeding.
While pregnancy is possible with these myomas, we usually recommend removal because the surgery is relatively easy and the results are favorable. Rarely, scar tissue can be a complication and sometimes the cases need to be repeated if it’s hard to get every little bit out at the first case.
Most doctors recommend the removal of submucus myomas, even if small.
Here is another easy one. What if you have one 3 centimeter (cm) (3 cms is a bit bigger than one inch) fibroid that is not growing near the lining, and it’s your only fibroid.
In this case, you do not need surgery.
Every doctor has his or her own size cutoff, but for almost all of us, 3 cm is just too small to operate.
Yes they can grow during pregnancy, but many do not.
Most doctors do not recommend surgery for 3 cm fibroids, as long as they are not in the cavity (submucus).
Now it’s going to be a bit harder.
What if you have 3 fibroids that are 3 cm each?
Or one fibroid that is 6 cms, or 7 fibroids all less than 2 cms?
These are the cases where the real answers are hard to come by.
Maybe you need surgery, maybe you don’t. And what does need mean?
Does it mean you can’t get pregnant without surgery? Does it mean you could get pregnant but then have an early miscarriage? Or does it mean that all will be well until the 28thweek of pregnancy when you prematurely deliver?
This is all impossible to predict. Every fibroid is different and every uterus is different. In addition, there are so many causes (not all known) of infertility, miscarriage and premature delivery that blaming the fibroids on bad outcomes is at times futile.
Many doctors have just a firm size cutoff, which could vary from 4, 5, 6, or 7 cms depending on the doctor. Some doctors, don’t use a cutoff, they use many multiple factors including size, location and history. Either way, we never really know, except in the most obvious cases, if the surgery we did made the difference.

I realize this can be a difficult part, and here is where the broken record comes in, get different opinions.
In the case of fibroids, opinions from high-risk obstetricians are very helpful. These are the doctors who take care of women with problem pregnancies, and they have a good understanding of the possible risks associated with fibroids.
I have found that these types of doctors are more comfortable with taking care of women with fibroids, but see that your doctors say.Next time we will talk about other conditions such as polyps and endometriosis.Of course any real opinions of you condition and options will have to come from your doctors. Dr. Licciardi

 

References:

  • Fibroids:
    • American Association of Gynecologic Laparoscopists (AAGL): Advancing Minimally Invasive Gynecology Worldwide. AAGL practice report: practice guidelines for the diagnosis and management of submucous leiomyomas. J Minim Invasive Gynecol. 2012 Mar-Apr;19(2):152-71.
    • Giatras K, Berkeley AS, Noyes N, Licciardi F, Lolis D, Grifo JA. Fertility after hysteroscopic resection of submucous myomas. J Am Assoc Gynecol Laparosc 1999 May;6(2):155-8.
    • Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. Am J Obstet Gynecol. 2008 Apr;198(4):357-66.
    • Munro MG. Uterine leiomyomas, current concepts: pathogenesis, impact on reproductive health, and medical, procedural, and surgical management. Obstet Gynecol Clin North Am. 2011 Dec;38(4):703-31.
  • Endometriosis:
    • Marcoux S, Maheux R, Berube S, et al. Canadian Collaboration Group on Endometriosis. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Eng J Med. 1997; 377:212-22.
    • Jacobson TZ, Duffy JMN, Barlow D, Koninckx PR, Garry R. Laparoscopic surgery for pelvic pain associated with endometriosis. Cochrane Database of Systematic Reviews: 4, 2009.
    • Fayez JA, Vogel MF. Comparison of Different Treatment Methods of Endometriomas by Laparoscopy. Obstet Gynecol. 1991; 78: 660.
    • Gruppo Italiano per lo Studio dell’Endometriosi. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Hum Reprod. 1999; 14(5): 1332.
    • Vercellini P, Chapron, C, Di Giorgi, O, Consonni, C, Frontino, G, Crosignani, PG. Coagulation or excision of ovarian endometriomas. Am J Obstet Gynecol 2003; 188(3):606-10.
  • Polyps:
    • American Association of Gynecologic Laparoscopists. AAGL practice report: practice guidelines for the diagnosis and management of endometrial polyps. J Minim Invasive Gynecol. 2012 Jan-Feb;19(1):3-10.
    • Rackow BW, Jorgensen E, Taylor HS. Endometrial polyps affect uterine receptivity. Fertil Steril. 2011 Jun 30;95(8):2690-2.
    • Bosteels J, Weyers S, Puttemans P, Panayotidis C, Van Herendael B, Gomel V, Mol BW, Mathieu C, D’Hooghe T. The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review. Hum Reprod Update. 2010 Jan-Feb;16(1):1-11.
    • Varasteh NN, Neuwirth RS, Levin B, Keltz MD. Pregnancy rates after hysteroscopic polypectomy and myomectomy in infertile women. Obstet Gynecol. 1999 Aug;94(2):168-71.

Fred’s Face Part 2

Hello everyone, in today’s blog you will see that I had to make decisions about my health. Yes, I am a practicing physician, but injuries of the face are not my forte. I received very different opinions from different doctors and I had to put it all together, which was not an easy task.

I am sure that many of you have been or are in the process of making a serious decision based on the information you receive from doctors. One main point here will be you always need to get another opinion. In addition, just because a doctor is well known doesn’t mean he/she will do the best thing for you.

The CAT scan revealed that I indeed had multiple fractures of my face, the most prominent being the zygomatic arch, which is the bone between your ear and nose right under the eye. It’s the one that gives your cheekbone a nice round shape. After notifying me of my results, the ER doctor, who was very nice and competent, told me I was probably looking at surgery with plates and pins.

By the way, a word about nausea. I have always been taught that when treating patients, nausea is worse for them than pain, and from this experience I can fully attest to that. As the blood filled my sinuses, I had tremendous nausea. When the doctor offered me pain medications I refused. I told him it really hurts but if the Percocet will make me even more nauseous I will not take it, I’d rather be in pain. He gave me something for the nausea, and I began to feel human, then I took the pain medication. I can also say from personal experience that the only time this concept may not apply is in the case of a kidney stone, which involves pain and nausea, but the pain is so insanely severe, pain meds first please.

Anyway, I was discharged from the ER, CAT Scan and drugs in hand, and off I went to seek professional help. I called a plastic surgeon friend who told me nothing needed to be done right away, so that gave me reassurance that I had some time to get to the right person. You should take your time too.

I did a bit of research and made appointments to see to 2 prominent facial surgeons, each at different institutions. Teaching point: I didn’t see one then decide to see another, I went for 2 opinions from the start.

Doctor One. Asshole. Typical NY office: all of the NY’s best this and best that plaques. Alright, I seem to be in the right place. Plus he was highly recommended, so let’s see where this takes us. He seemed nice, thoroughly examined my CAT scan, and then told me what I absolutely needed, no question about it. I needed to have the bones put back in their right place with pins and plates. Because some of the broken bones were part of my upper jaw, he said that if I did not have the surgery I would never be able to eat properly again. To get to the bones, he would need to make a long incision right across the front of my face. Not a word about the resulting scar. He was so interested in doing the surgery, he called the hospital and resident right in front of me and scheduled me for Sunday. Who does surgery on Sunday? Who rushes to get the thing booked right away? Someone desperate to operate, that’s who. He already knew I was getting other opinions, so after hearing this I said I would get back to him. I did not totally dismiss his suggestion, but I left his office running. And he was the most prominent surgeon at a very fancy New York Hospital.

Doctor Two. Better, but, well you’ll see. Same thing, the good recommendation, plaque city. He was a very nice man, who seemed much more competent that doctor one. He reviewed my films and told me that I had the option of surgery or no surgery. If I had surgery he could do it from the inside of my cheek. Wow what a difference; imagine how angry I became at doctor one who had no problem at all slicing my face right open. I am still mad at him. Doctor 2 was not worried about the eating thing, getting me even madder at Doctor 1. Doctor 2 did however say that he was in favor of surgery. Why? “Because afterwards I would be more beautiful.” More beautiful? Is he kidding? Here I was 50 years old, married 24 years and he is telling me I should have the surgery to be more beautiful? I think he must have dosed off during our conversation and he forgot I was not coming in for a facelift. Then when I asked him again about a scar he did say that some time after the original surgery he would need to make a tiny incision on my face to remove a wire. Oh.

Two doctors 2 very different opinions. At least I felt safe with Doctor 2, so if I thought I should have the surgery, I was fine with him doing it.

So as it turns out I have a friend through a friend who is also a prominent facial surgeon, Steven Denenberg. He practices in Omaha, but with the internet and phones, I was able to send him my films and talk about my options. With Steve, things were starting to make sense. The key approach: think about what you have now, and how that might be changed with surgery. What did I have? A depressed face, pushed in about 2-3 millimeters, enough to see if you looked carefully, but to most people, not noticeable. What would surgery do? It would give me a risk of bleeding, infection, big or small scar, and may or may not be able to make a big difference in the way I looked. What if in the quest for perfection, the doctor raised the bone 2 mm too much? This is a real possibility because it’s hard to get it exactly right with such small distances. What if in healing it only really elevated one millimeter? Then it was kind of a waste to have the surgery in the first place.

So in the end, I did not have the surgery. When I look in the mirror, I see the dent, but I’d rather see the dent than a massive scar or some other bump or new dent from surgery that was supposed to make me better. And years later I am still eating, no one has ever noticed my slightly asymmetric face, and I have not missed out on any movie roles for being less beautiful.

Has a doctor recommended surgery to you? Do you have fibroids, endometriosis or uterine scaring? Next time I will do my best to discuss which surgeries may be necessary and which are not.

Thanks for reading, I’ll write again soon,

Dr. Licciardi

Fred’s Face Part 1

Hello everyone. I will start today with a story that at first is not related to infertility, but in the end will provide a discussion that will be relevant. Here we go.

Well here you see it, the spoils of a surfing accident that in 2007 changed my face just a bit just forever.
I really had to force the smile here because I was in pain and sleepless. Surfing accidents are usually quite embarrassing. They are frequently caused by human error.
This could mean 2 crashing into each other, in which case one party was in the wrong, but even here the person in the right may have avoided injury if he was paying more attention to his surroundings. In most other cases, the surfer gets into trouble for not properly thinking about the task at hand ie. trying to catch too big a wave. Commonly, it’s just a matter of improperly judging the break of the wave or improperly timing the standup and turn. Sometimes poor judgment relating to local conditions ie. reefs, shallow bottoms, currents etc., can get surfers into big trouble.
The point is surfing accidents are never glamorous.

It’s not like saying “I broke my arm running with the bulls”. Skiing accidents are more suitable for putting the blame on something other than stupidity. “There was this huge patch of ice”, “they did not groom well” and “my binding never released” are common statements lifting the blame for injury away from the operator.
When you get hurt surfing, you usually know what you did wrong, and it’s not a good feeling.My main problem was inexperience.
I grew up spending a fair amount of time in the ocean and frequently body surfed and boogie boarded, so I was at least familiar with wave shapes, currents and tides. But I did not start surfing till much later and without lessons I was just out there waiting for trouble. Learners tend to start on larger boards, and mine is a monster.
9 feet 6 inches of very thick glass, making it one of the heavier boards in its class, quite a torpedo. Perfect for learning and for getting up on small waves, but dangerous under the wrong circumstances.

So this is where the non-glamour comes in.

I wasn’t even trying to catch a wave.
I paddled out on a rough day with wave that were closing out, meaning that the wave instead of starting to break on one side, the wave just broke all at once, not leaving any place to catch and ride. After a while I recognized this and realized I should head in: good thinking. What I did not appreciate is that you need really watch the waves as you come in, because if you get caught at the wrong spot, a large heavy wave can crash right on top of you sending you and your board, separately of course, into the underwater equivalent of outer space.

You go down and around and around and around.

So that’s what happened to me.

Knowing my board was not far from me, I covered my face with my hands (I have since learned arms are better) and I waited for the rough water to calm. Just as moved my hands away, while still well underwater, the nose of the board rammed into the side of my face, hard.Why am I telling you this? Because I want to tell you of my experience with the doctors I ran into in seeking treatment. My interactions were probably very similar to yours, especially when faced with the prospect of surgery. And believe me; I was very surprised by what I found.

All to come in the next blog.

Clomid vs Letrozole: The Last Words

Hello everyone! Today I will conclude the entries on Letrazol and Clomid, emphasizing the warnings related to letrazole.

“Femara* (the trade name for letrozole) is contraindicated and should not be used in women who may become pregnant, during pregnancy and/or while breastfeeding, because there is a potential risk of harm to the mother and the fetus, including risk of fetal malformations.”

Who says so? Novartis, the company that makes the drug, put out this warning.

There are 2 elements to this statement. First and accurately, the drug has been shown to cause malformations in mice and rats when given in low doses during pregnancy. If is for this reason that we all believe that giving it to pregnant women is not indicated. Clomid also carries a warning that it is not to be used in pregnancy for fear of birth defects, although the potential for defects seems to be lower than for Femara. Nonetheless, Clomid carries a warning.

The second element has to do with taking the drug before pregnancy, as in the case of induction of ovulation. In 2006, the company issued a statement to physicians specifically stating that Femara is not indicated for use in the induction of ovulation.

How did this second statement from Novartis come ot be? In 2005 a very short abstract was presented at a scientific meeting showing the birth defect rate was higher in 150 women who took Femara as compared to the general population. That’s 150 births, not 150 birth defects. Now, no one wants to ignore important birth defect data, however 7 birth defects in 150 women is just too small a group to rely on. Based on this one preliminary study, Novartis quickly issued the warning to physicians.

Soon after the Novartis letter, another physician, Dr Tulandi, examined pregnancy outcome of 911 babies conceived after Clomid or letrozole treatment in infertile women. Here is the data directly quoted from the writings of Dr.Tulandi. “Overall, congenital malformations and chromosomal abnormalities were found in 14 of 514 newborns in the letrozole group (2.4%) and in 19 of 397 newborns in the CC group(4.8%). The major malformation rate in the letrozole group was 1.2% (6 of 514) and in the CC group was 3.0% (12 of 397). These differences did not reach statistical significance because of the relatively small sample size.”

Well then, it seems that clomid has a birth defect rate that is at leat equal to that of Femara, and yet Clomid is used much more and without and warnings. The point being that the early small study was not informative enough and Femara seems safe to use, at least as safe as Clomid. Now this second study was not perfect either, but it was bigger and better than the first.

These are not the only studies published on Femara. There have been dozens all showing that the drug can be very effective and none others have shown an increase in birth defects.

Why would the drug company want to sell Femara if there is controversy over its safety?

As we discussed previously, Femara is a medication that blocks estrogen production, which is very helpful for many women with breast cancer. Most women have the type of breast cancer that grows faster in the presence of estrogen. Blocking the body’s ability to produce estrogen using Femara can significantly slow the growth of the tumor. This is why the company produces the drug. Unfortunately, there is a tremendous market for such a product.

On the other hand, the fertility business is comparatively very small and it is associated with very large liability risks. Even if the data relating the drug to birth defects is poor, I can see why the company would want to protect itself from potentially crippling birth defect lawsuits.

The good news is that the drug is available and a licensed MD can prescribe any drug “off label”, as long as there is good evidence that the drug is helpful and there is no harm.

Tons of drugs are used off label. One fertility example is Lupron for endometriosis. This drug is mostly used to treat men with prostate cancer as it lowers testosterone levels which may help restrict tumor growth. Lupron is also used in women with endometriosis because it lowers estrogen levels, and endometriosis needs estrogen to grow. Many women take it and the literature is loaded with scientific articles supporting its use in medical studies. And yet, Lupron it not FDA approved for the treatment of endometriosis. (For those of you thinking ahead, yes Femara is used by some to treat endometriosis). Another example is the use of antiepileptic drugs to treat anxiety and depression. Believe me; the list goes on and on.

So where does this all take us?
1) Femara works for the induction of ovulation.
2) Femara should not be given during pregnancy.
3) Femara does not thin the lining of the uterus as may Clomid
4) Femara is relatively new and associated with more warnings.

It is the last statement that makes doctors understandably nervous about using it, especially when there is a close alternative (Clomid) that has been around since the 1960’s.

As time has gone by, I have used Femara more and more, but still use Clomid first. As more time passes and more studies are done, this may change, and it is possible that Femara may become the first line treatment over Clomid for all fertility doctors. Importantly, no one yet has proven that Femara leads to a higher pregnancy rate than Clomid.

Thanks for reading and don’t forget to read the disclaimer from 5.17.06.

Dr. Licciardi

References:

  • Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5.
  • Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril. 2002 Aug;78(2):280-5.
  • Legro RS, Kunselman AR, Brzyski RG, Casson PR, Diamond MP, Schlaff WD, Christman GM, Coutifaris C, Taylor HS, Eisenberg E, Santoro N, Zhang H; NICHD Reproductive Medicine Network. The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemp Clin Trials. 2012 May;33(3):470-81.

Clomid and Letrozole Part 2

Now a bit more about Letrozol (also known as Femara). Letrozol and Clomid have the same end result: ovulation, but they go about it in a much different way. Letrozol acts by decreasing the body’s ability to make estrogen, whereas with Clomid estrogen is produced but its actions are blocked.

Letrozol is an aromatase inhibitor. Aromatase is the enzyme that makes estrogen. Now there are many steps to making estrogen, but aromatase is the last and most important step. Aromatase takes testosterone and slightly changes it to become estrogen. Yes, women have some testosterone, but men have more. To me it’s amazing that testosterone and estrogen, two hormones that are so different, are just one step away from each other. Nevertheless, that’s the case and the system somehow works.

As Letrazol inhibits the formation of estrogen, estrogen levels fall. And this helps women become pregnant? Crazy as it sounds that answer is yes, and this happens in a way similar to the workings of Clomid. Once again, the brain sees no estrogen (this time because there really is very little). The brain reacts, and puts out more FSH to stimulate the ovary to make estrogen, which the ovary can only do my making a follicle, that just so happens to contain an egg. Just as with the Clomid, the follicle grows, the egg matures and ovulation usually comes next.

How can you get pregnant if you are taking a drug that is blocking (Clomid) or eliminating (Letrozol) estrogen? You do not need estrogen to ovulate. Estrogen is a buy-product of the growing follicle. The reason estrogen is made by the follicle is so that the lining of the uterus (the endometirum) can grow. And yes you need the endometrium, but for most women only a small amount of estrogen is needed to get a good lining. Plus, the aromatase inhibitors do not make the estrogen go to zero, and Clomid does no completely block estrogen. These drugs may cause the endometrium to see much less estrogen than usual but enough gets through for adequate growth.

In addition, Letrazol and Clomid are only taken for 5 days, usually until day 7-9. This leaves 5-6 days for the follicle to grow a bit more and produce more estrogen, all while the drugs are leaving the body.

There are some differences in the negative effects between Clomid and Letrozol. Clomid has a long half life meaning it stays in the body for days after the last dose. Its half life is 5-7 days, so blood levels go up and up each day the pill is taken and significant amounts are present around ovulation. Therefore conditions around the time of ovulation can be effected by the Clomid i.e. the cervical mucus can be too thick and the lining of the uterus can be too thin. The half life of Letrozol is shorter.

The good news is that for most women these drugs work quite well. We do not know why some women have more side effects than others. Subtle genetic differences between women lead to very subtle differences in the shapes of one or more of the proteins involved in binding.

Letrozol also has fewer mental side effects. Common Clomid side effects include headaches, hot flashes, depression, seeing spots, jitteriness, trouble sleeping, and there are a few others. Letrozol does not cause as many of these symptoms.

If Letrozol seems to be better for the mucus, lining of the uterus, and has fewer side effects, why don’t we use it as our first line of therapy over Clomid? This requires a little more discussion which will come in the next entry.

Thanks for reading and don’t forget the disclaimer 5.17.06.

Dr. Licciardi

References:

  • Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006 Jun;85(6):1761-5.
  • Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril. 2002 Aug;78(2):280-5.
  • Legro RS, Kunselman AR, Brzyski RG, Casson PR, Diamond MP, Schlaff WD, Christman GM, Coutifaris C, Taylor HS, Eisenberg E, Santoro N, Zhang H; NICHD Reproductive Medicine Network. The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemp Clin Trials. 2012 May;33(3):470-81.

Clomid vs Letrozole

Hello everyone, here we are with the latest installment of The Infertility Blog, which will discuss the differences between Clomid and Letrozole.

This one is a little medical, but I think I can get everyone through it just fine. I’ll start by saying both do the same thing, they both stimulate ovulation, but each does it in it’s own way. Both are pills, both can work great in women who are anovulatory, both work only fairly well for regularly menstruating infertile women. Let’s go over Clomid first. The generic name of Clomid is clomiphene citrate. It also goes by Serophene. Clomid is a drug that has been around since the 60’s.

In the lab it was discovered that this compound blocks estrogen. This does not sound like a good fertility drug if it’s blocking estrogen. In fact the developers thought that since it blocks estrogen , it may be a good contraceptive. Well it had the opposite effect. Why? After swallowing Clomid, it gets taken through the blood stream to all parts of the body, including the brain. The brain is important because that is where all of the control of ovulation starts. Normal ovulation can not happen without signals from the brain and pituitary gland. When Clomid, the “anti-estrogen”, gets to the brain, things start happening. More about this in a moment, first a bit about how estrogen works.

Estrogen, like all hormones, exerts its influence by landing on a receptor. A receptor is a protein either on the surface or inside the cell that recognizes a hormone and binds to the hormone. It is the receptor/hormone combination that then causes the cell to do what the hormone says to do. For example, after estrogen binds to the estrogen receptor the combined hormone/receptor can get the cervical cells make mucus for example. It’s very much like a lock and key. The estrogen is a key that only works in the estrogen lock (the estrogen receptor). Other hormones, like progesterone and testosterone, float around and then only bind with their receptors. Like a key, different hormones have slightly different shapes, and the receptors will only connect with a hormone if the hormone has the right shape.

OK, back to Clomid and the brain. When Clomid gets to the brain, because the Clomid molecule has a similar shape as the estrogen molecule, Clomid binds to the estrogen receptor. But because the shape of the Clomid molecule is not exactly the same as the estrogen molecule , the estrogen receptor Clomid combination is faulty, and can not signal the cell to do anything. Elsewhere in the body, the cervical cells will not make mucus. for example. The Clomid takes up all of the available places on the receptor so that the estrogen has nowhere to land, thus the actions of estrogen are blocked.

No estrogen, that is what the brain thinks. The brain says, “Hey, what happened, who turned off the estrogen?” So the brain tries to make more. Estrogen only comes from the ovary, with a few small exceptions, so the only way for the body to get estrogen is to stimulate the ovaries to start ovulating. This is accomplished by the brain stimulating the pituitary gland to put out bursts of FSH, which then travels through the blood stream to the ovaries and gets ovulation going. For most women, this estrogen block is not 100%. Its enough of a block to get ovulation going, but usually the Clomid can spare complete havoc the endometrium (uterine lining) and cervical mucus. In some women, but a small percentage, there is complete havoc; the cervical mucus completely dries up (overcome by insemination) and the uterine lining becomes too thin (can not be overcome). This is why some doctors give estrogen and Clomid at the same time.

It is believed that the Clomid will get the ovulation started and the given estrogen will counteract the Clomid in the uterus and cervix. I have not had much success with this method. I have found that if the Clomid creates havoc, adding estrogen does not help. Clomid works wonders for women who have irregular cycles, Clomid allow for more frequent, predictable ovulation, and this ups the odds of conception. Women with PCO are excellent candidates for Clomid because they have irregular cycles, which could be anywhere from every 35 days to every 6 months to never. Women who have irregular cycles but are not exactly PCO also have excellent results with Clomid. Women who do not get their periods due to exercise, eating disorders or other types of women with “hypothalamic amenorrhea” usually do not respond to Clomid.

This is because their brains do not respond to the Clomid because the brain knows that if there is severe stress or no food coming in, it’s not a good time to get pregnant, so even clomid will not work. We ask women to take Clomid (and letrozol) early in the cycle because we want to give the boost in FSH early so that maybe we can coax the ovary to make more than one egg that month. FSH rises from Clomid, and it’s the FSH that really does all of the work to initiate ovulation. In women who get periods every 4 months, it really does not matter if Clomid is given days 5, 10 20 or 30. We would prefer if you were not pregnant when taking Clomid (although it happens and probably not a problem), that’s why we wither give Provera to bring on a period or do a pregnancy test before you start. So that’s a little about Clomid. It works by blocking estrogen from it’s receptor. More to come next time.

Thanks for reading and please read disclaimer 5/17/06.Dr. Licciardi

References:

  • Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in women. Fertil Steril. 2003;80(5):1302.
  • Hughes E, Collins J, Vandekerckhove P. Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev 2000; CD000057.

Back to School, Back to Questions

Hello Everyone! I hope you had a nice summer.

I’m going to start the fall off with answering some very interesting and important questions. Then I have the next few blogs already mapped out. Here we go.

PCOs. Can you have PCOS if you have regular cycles and no symptoms, just ovaries that have many follicles? No, you need to have one other symptom: irregular infrequent periods or androgen excess, the later being demonstrated by increased facial/body hair, acne, or more rare symptoms. I frequently see women who have healthy ovaries on ultrasound, meaning they look good because they have many follicles, probably enough to fit the criteria for PCOS. But without the other symptoms, these women are just lucky.

Uterine Abnormalities. If your uterus is bicornuate or dydelphic, a singleton is highly preferred over multiples. Sometimes the best way to achieve this is by having IVF and a single embryo transfer.
FSH. If you were told you have a high level, you must repeat the test. Odds are that the results will be similar; however that is not always the case. I’ve seen many women who were dismissed from other practices for having high FSH levels only to have better results on repeat: some became pregnant.

Amenorrhea. If your ovulation stopped due to weight loss, it may not return after weight gain. We don’t know why, but in some but not most cases, the changes in the brain that occur with weight loss become permanent. I am not sure about the term Ovarian Insensitivity, I would get another opinion.

Endometriosis. Most doctors today do not do a laparoscopy on women who just started trying and have no evidence of endometriosis. Evidence means very painful periods and or visible cysts of endometriosis on the ovaries seen on ultrasound. If the hysterogram is normal, i.e. the tubes are open, and the history and findings do not point to endometriosis, the odds of finding significant endometriosis on laparoscopy are very low. This does not mean you can’t have the laparoscopy if you wish, but in most cases it is recommended only as an option.

Ectopic Pregnancy. If during IVF, embryos are placed in the uterus, how is it possible to have an ectopic pregnancy in the tube? Unfortunately this does happen, probably because the embryos float into the tube sometime after the transfer. The uterus is a muscle and this muscle does undergo slight but regular contractions. It’s possible that the embryo gets squeezed up into the uterus. There are fewer ectopic after IVF these days, for a few reasons. One big one is that we put in fewer embryos these days. Fewer means there are lower odds of one ending up in the tube. Another is that many women who need IVF because of big blocked tubes (hydrosalpinx) have these tubes removed prior to IVF. A hydrosalpinx is a swollen tube damaged from infection, very severe endometriosis or previous surgery. The interior of these blocked tubes becomes damaged, making ectopics more likely.

Cervical Mucus. Most infertility doctors are not concerned with cervical mucus. We all understand that women who have no treatment or minimal treatment get pregnant on their own. Some women who get their mucus in some way adjusted get pregnant, but the rate of pregnancy may not be higher than baseline.

Thyroid. So far there is no good evidence showing a relationship between thyroid abnormlaites and embryo quality. Certainly, the thyroid should be close to normal while attempting and during pregnancy. It is very difficult to get accurate TSH level during IVF stimulation because during and IVF cycle, the estrogen levels become higher than normal, and this interferes with accurate assessment of TSH.

Embryo Quality. Are poorly growing embryos more likely to be genetically abnormal? The answer is yes, but not by much. This means that the way an embryo looks is not tightly related to chromosomal normality. A poor looking embryo is a little more likely to be genetically abnormal, but you can’t count on it. So if your best embryos are slow growing, we transfer them.

Early Pregnancy Failure. Women with pregnancy losses should have a karyotype, which is the blood test done on both partners to check for possible chromosomal abnormalities. Another necessary test is the hysterogram which will test for uterine abnormalities.
Should women with repeated loss keep trying on their own, do fertility drugs and iui, or move to IVF, possible with PGD? This one of the most difficult questions in our field. I tend to feel that if you are getting pregnant easily on your own, keep trying on your own. However, there is a place for IVF with PCG depending on your situation and age. Certainly finances come into play.

Cervical Stenosis. Usually improves after a vaginal birth because the cervix stretches so much. If the baby is born via c-section, the cervix may not have opened enough to make an improvement. Sometimes even in women without stenosis, healing post c-section can greatly increase the angle between the cervix and the uterus. This is not really stenosis, but this acute angle can make it very difficult to get a catheter, say for iui or embryo transfer, from the cervix into the uterus.

Anti-sperm antibodies.
Most fertility doctors these days do not see a relationship between anti-sperm antibodies and infertility. If these antibodies are a factor, most of the time the antibodies that are the biggest problem are those that are in the cervical mucus. The antibodies in the mucus grab the sperm trying to swim through. Therefore, avoiding the cervical mucus via iui can do the trick. You do not need to take fertility drugs if it is felt your only problem is antibodies; an iui without the drugs may suffice.

Uterine lining.
All experienced fertility doctors have many women who have become pregnant with “thin” linings. No one knows what the cutoff should be. One problem is that the studies are not done correctly. For instance, let’s say an IVF program analyzes their pregnancy rates according to the thickness of the uterine lining. What happens is the different thicknesses become grouped. They may look at pregnancy rates for women with linings greater than 10mm, 7-10 mm and less than 7 (this is just one example: some may do >9, 6-9 and <6, or any other way they wish). The problem with this is less than seven includes women with 4s and 5’s. So to say less than seven is a cutoff may not be accurate because the pregnancy rate at 7 may be just fine, but it will be lower in women with 4’s and 5’s, but they are all grouped together. The reason the studies are not set up as the pregnancy rates for 6 mm and 7 mm and 8 mm etc. is that the overall number of women in each study is small, so number of women in each group becomes too small to calculate a difference. Why is my lining thinner today than yesterday? This is very common. The most likely reason is that the lining was measured in a different location on each day. When we scan, we quickly look for the thickest part and write it down. Most fertility doctors are not really interested in progression from day to day. If we glance at it and it looks ok without even measuring it, we quickly find a spot, any spot, and get a measurement. Another reason for differences is that you may have a different person measuring on different days. Different people may measure differently; the measurement should be close, but not exactly the same.
Another possibility is that the lining grows and shrinks a little from day to day. I’ve noticed, usually in cases where the lining is thick, that linings change from day to day. The lining does usually grow thicker as the cycle progresses. Sometimes there is a quick growth such that by day 7 it’s nice and thick and stays at about that level through the next week or so. Sometimes the lining is thin on day 10, but after 2-3 more days it has a late improvement and looks great.

AMH. How can your FSH level be normal and you AMH be very low? Because we don’t know yet what normal and abnormal levels of AMH are. The values also vary considerably from lab to lab. I have not yet started doing AMH levels for this reason. I have seen levels of 0.16 along with FSH levels of 7 in young women. In some labs, over 1 is good, I others lower levels are normal. More time is necessary to work this one out.

Ovulation Induction. You can get pregnant in an iui cycle if the follicle is 16 mm. It’s a little on the small side, but in most cases it’s big enough. One reason we wait on a 16 mm follicle is that there may be others that are even smaller. In those cases, we much prefer to wait.

IVF Failure. Are there some women who will just never get pregnant? Unfortunately the answer is yes. But we have no idea in advance who these women are, unless there is an obvious reason for their infertility. There probably a few men or women who have a hidden untestable genetic problem that prevents pregnancy. Some women just can’t catch a break. They have problems that seem correctable with surgery or IVF, but they don’t get pregnant, or they have miscarriages. It’s a terrible cast, one of many that life sets us into.

IUI Clomid at 41?
Cross my heart, we have a woman in our practice that got pregnant and had a baby at age 47 on clomid, after every other treatment under the sun. That being said, taking clomid in your 40’s may not be the best thing. Even with iui, the odds are less than 5%, and every month you are not pregnant, you are one month older.

Blastocyst Transfer. Would embryos that stop growing from day 3 to day 5 have been better off getting transferred on day 3? It depends on the experience of the IVF clinic. At NYU we are very experienced and successful with day 5 (also called blastocyst) transfer. I feel very confident that the lab is as good as the uterus from days 3-5. Very rarely I have a patient who I prefer to transfer on day 3. This is happens when the embryos look close to perfect on day 3 but terrible on day 5, a very rare occurrence. Many IVF programs are not as experienced or successful with culturing to day 5, and in these cases, a day 3 transfer may be better.

Agonist vs Antoginist. (Lupron vs Cetritide or Ganirelix). I use some but not much lupron anymore. One reason has to do with patient convenience; lupron is just one more shot people have to take. Cetritide and Ganirleix are given by injection, but only a few doses are necessary. Plus lupron can cause an ovarian cyst to grow interfering with the timing of the cycle start. In some cases, especially in older women, I believe that lupron can suppress the number of developing eggs. But the lupron protocol is still one that I go to at times.

Low estradiol on day 3? Hard to explain why the level is so low if you are having normal ovulation. If indeed you are having normal ovulation and respond with normal estrogen levels to fertility drugs, the low level on day 3 may not be a problem.

7 miscarriages. Very sorry to hear of your problem. I assume you both had karyotype testing. You may want to consider IVF with PGD. I understand that there may be financial barriers to that service and doing IVF/PGS does not guarantee pregnancy much less a successful pregnancy.

2 Miscarriages after IVF with good egg number and nice embryos.
Talk to your doctor, it sounds to me like things can happen in the positive for you.

Thanks for reading and don’t forget to read the disclaimer 5/17/06.
Dr. Licciardi

Tension

Hello again to everyone.

Tension is the pressure that slowly builds up around us and within us. It’s a pressure that begins on the outside, sometimes very far away, but it somehow finds its way inside us. At first it’s not perceivable, then we notice something but don’t quite know what it is. Then, as things build further, we know what is but want to ignore it. Then and after feeling things are mostly out of hand, we finally we admit to ourselves that yes, we are wound dangerously tight. Some of us are good at then identifying the problem and fixing things back at the source. If things are unfixable we find another controlled and logical way to release the stress. And some of us are not good at identification and self correction, so we just explode, usually after it’s too late. Either way, if we could at least detect the problem earlier, or at least see that there is a problem earlier, we could make things better in the end. Sounds easy.

Over the past week I have been thinking of a few of my own interactions with tension, and helpful things I have heard from others. The key here is betting in better touch with the early signs that tension is brings to your body. Even the least amount of mental tension gives us physical tension. Noticing the physical tension early, so that an early correction can be made, will do wonders for relieving the mental tension. I’ll use a few very simple non-fertility related scenarios as examples of little ways we can understand ourselves better.

1) Some of you may know that I practice Bikram Yoga. It’s not a religion for me, I get there when I can. Frankly, I don’t really love being there. But I was born remarkably inflexible, so I do gain a tremendous benefit, primarily improving my performance in a slew of recreational activities. Bikram also builds strength around the joints, a few of which are in disrepair. During a yoga practice, the instructor typically leads the class through a number of positions, the order of which is deliberately organized. For each position there is the ideal form and degree of bend, and the instructor goes through a list of points for the body and mind directing the students towards these goals. Of course most of us are far from ideal, but getting close, or closer, is quite a workout. If you are involved in formal instruction of any type i.e. music languages, sports; you have recognized that instructors repeat the same thing over and over. Even after months or years into practicing we still are told the same things. This works because as we progress, we hear things differently and eventually things start to click, but it really may take quite some time. So this week, in the middle of my 90 minute class, I am putting on my usual miserable display of form, and sweating insanely. Vowing to stick with it, I strain to align my body and put body parts in places they should never be. Obviously struggling, the instructor says, “relax your face”. “My face, my face? “I say to myself, “are you crazy, my face is the last thing on my mind right now.” But then, after hearing it now for probably the 200th time, it finally made sense. I relaxed my face and my whole body followed along. So the point here is when you feel the infertility tension perking up, check you face first. It may be difficult to melt your body stiffness instantaneously, but the face is more controllable, and if you can start there, the something good may follow.

2) Most of you don’t know that I like to play golf. I play well enough to move along but that’s about it. I like to sink my teeth into my hobbies, so I try to get in a few lessons and practice here and there. Like many players in my bracket, non-relaxation can be a big problem. Last time out I noticed something that I hope will help me considerably. I found that while waiting to tee off, my shoulders were so shrugged up that they almost were touching my ears. There was absolutely no reason for me to be in such a knot. But in anticipation for my next shot, I was doing something that was only making things worse, and until that day, I had no idea it was even happening. I still do it, but I catch myself and let my shoulders fall, which makes me feel better and may, let’s hope, help my game. So try to be conscious of your body in stressful times. Maybe there is muscle group that is acting out, without you being aware. Maybe you sit in an uncomfortable position or bend you back in an awkward way. When the body is out of kilt the mind is right along with it. Taking away hidden physical tension will free up some of the mental tension. Now it would be nice if we could just release the mental tension first so that our physical tightness could resolve, but we all know that is not the reality.

3) Many of you may know that I love to ski. Of all my many little distractions, skiing is my favorite. Over the years I have been involved with ski clubs, ski groups and lessons. One day I was working with a coach and I was in the starting gate for an amateur race. I put my poles over the timing wand, visualized the hill and turns, bent back and awaited the countdown. My coach, who I didn’t even think was watching, looked over and said, “for how long are you going to hold your breath?” That was a big awakening for me. As I prepared for my start, I was doing everything except the most important thing: breathing. How is it possible to initiate a mentally or physically challenging task without oxygen? Not only should we breath, we should take in extra strong deep breaths ahead of time to make our bodies really ready for whatever job is at hand. Getting in shape involves having our bodies become accustomed to an increase in demands, but half of that is just getting our lungs to work earlier and faster to get the air in. Tension pulls away our awareness of basic breathing. Then, after becoming oxygen starved we become more tense irritated and short tempered, all while we have no clue as to what even is going on.

So that’s it for today. Three little personal vignettes relating tension to body tightness and breathing. I used examples related to athletic activity, but the principals apply to having blood drawn, getting an injection or having an embryo transfer. It can even apply when talking to your boss, family member, contractor, and the list goes on and on. Try to pick up the stress signals as early as you can, and this will hopefully lead to easier traveling.

Thanks for reading,

Dr. Licciardi

Being Positive

Welcome back.

Well, as some of you may have guessed the previous story has a happy ending. While weighing her options Sheri became pregnant. 9 months ago she had a girl, and all is well.

I talked to Sherri about the whole ordeal. She reminded me that she had done many IUIs and 4 IVF cycles. She believes her success was aided by sticking with trying the old fashioned way when not in a medical/IVF cycle.

She is resistant to sayings like, “it’s easier to get pregnant once you stop with our doctor”. And she did want people to know that she did not change her diet or add any holistic therapies, it just happened. (Just a note about this. Of course I believe in the benefits of life-improvement techniques, but they may work best when used in conjunction with conventional therapies Using unconventional therapies alone has some, but limited benefit, and counting on them as you are aging is not recommended. If two groups of 41 year olds try holistic vs holistic plus fertility treatments, both groups will have pregnancies, but there will be more in the second group).

So what are my comments? Every infertility patient has a built in “on-your-own” pregnancy rate. People do get pregnant without treatment. For some the rates are very low, but as long as there is at least one tube and some sperm, the rates are rarely zero. Sheri had an edge; she produced an excellent number of eggs during her ivf cycles and this meant the overall status of her ovaries was well above average. Plus we all understand the Sheri is an exception, not the rule. The fact is, most women her age with a longstanding history of infertility do not get pregnant using their own eggs, even with the most aggressive treatments.

But when it happens it’s wonderful. Plus, in her case to get through the increased risk of miscarriage that goes along with being 43 is a big relief.

But why and how she did it may not be the most important point here. I think we should take time out to celebrate and hope that everyone has the potential to be successful as quickly and as easily as possible.

I’ve had a few other surprises in the past months. I have had my share of patients who responded poorly to the medications causing us to cancel their IVF cycles. With the few eggs that we had, we did an iui “just in case”. Sure enough, 3 women became pregnant and they are all doing well.

Two years ago I had a woman in her 40’s get cancelled from an FSH iui cycle. Her estrogen did not budge after 10 days on drug. Four weeks later her home pregnant test was positive and she had the baby. Apparently, her normal cycle started the day she stopped the injections and without even knowing she ovulated, and without monitoring or exact timing, she became pregnant.

And on the IVF side, I have one woman whose pregnancy is doing well despite her having her retrieval at age 45. Plus, I have had a slew of women whose embryos did not look very good at all, but went on to be successful.
And just yesterday I did a pregnancy ultrasound on a woman who did absolutely nothing except try. I met the couple about 3 months ago. He had a few medical problems that were resolving. Things turned around and they were successful on their own.

One point here is that busy infertility doctors, who promote surgery, fertility drugs, inseminations and in vitro, have many patients who get pregnant without their help. We suggest IVF to some who decide to do iui instead, and some of them get pregnant. We have older patients who have failed many cycles. We may ask them to consider other options, but they persist with IVF, and a few do get pregnant. We have women on our donor egg list who call to come off because they became pregnant.

I don’t want to confuse the luck of a few with the harsh reality of many. But I think it’s important to hear about the potential positives that do exist among people who did not have the best chances. Will being positive up your odds? Some say yes. If not, at least it will give you more strength as you continue on your difficult path.

Another person needs to be very positive, and that person is your doctor. I think most are. You need a doctor who is honest and can communicate the reality of your situation and the odds of success. If you and she believe it’s in your best interest to initiate or continue treatment, then she needs to be behind you 100%. Unfortunately, there are some doctors who do not have the correct mindset to be positive and an advocate for women whose odds are low. No one can really predict who will or will not get pregnant, so why not go in saying it will work. Your doctor should work with everyone as if they will be the one. Again, I think most infertility doctors are very good at this, but if yours is not, try another.

I don’t know if Sheri became pregnant because she was always positive. But I like using her as an example of how good things do happen to people who have one or more factors hindering their chances. Most infertility patients are not optimal candidates for success. Most patients have some barrier, known or unknown, to getting pregnant. Work with what you have, and good things may come your way.

Thanks for reading,

Dr. Licciardi

Update on a Past Story

Hello everyone once again.

Last week I received some new information about an old story, going back to August 2009. Here is the reprint of a past blog. Read it through, and soon I will post the follow-up information.

Dr. Licciardi

It wasn’t supposed to end this way. We all knew going in that nothing was guarantied, but we felt good and optimistic about starting. Together, we believed that if we just obeyed the rules and had faith, that good things can happen to good people. We anticipated sacrificing time, emotion and money, for a process that was logically the most reliable way to go. We figured it was the best option, and we were “all in” to work towards success.

Shari was 41 when we first met and she was already at it for more than a year. She was very smart and informed. Shari understood the small details of each treatment, but didn’t dwell on the negativity. She was super practical. The plan, which she started at 39, was to start with iui, and move to IVF if nothing happened. She eagerly and compliantly stuck to the plan, and had 2 IVFs under her belt by the time she first saw me.

At our consultation I definitely saw hopeful signs from her previous cycles. She made 15 eggs the second time. Plus her embryo quality was very nice. I explained that 3 things really help when you are trying to get pregnant with IVF at 41; a high egg number, good looking embryos and chromosomally normal embryos. We knew off the bat that she at least had 2/3. More eggs means more selection. We all know that a large percentage of embryos have bad chromosomes, so if you have more embryos, you are increasing your odds of at least one of them being normal. And if they look nice, all the better.

Wow, she called to tell me she got pregnant on her own. Sweet. But there was no heartbeat at 7 weeks, and she needed a D and C. This caused her to pause, and logically concluded that maybe FSH iui could work. So she tried to no avail.

Doing more IVF cycles was not an easy decision. She had some infertility insurance coverage, but that was all gone, so she had to pay for anything else, including the medications. But she weighed the options and decided to proceed with more IVF based on her good response, recent pregnancy and advancing age.

So off she went into her 3rd and 4th IVF cycle with me. Each time producing eggs and very good embryos. We changed the protocol a bit, but in the end she had cycles that most other women could not achieve.

Except for the two negative pregnancy tests.

And that’s the end of the story.

When we last spoke she was again very practical. She just didn’t see the value in going into a 5th IVF cycle. She could not afford donor egg. She was very kind, expressing her gratitude for the treatment she received. But this was it; she was done. She had ended her quest for a baby. Stated differently, she was probably not going to have a baby.

So why am I bringing this story to you, as this is not the first tale of woe in the infertility world.

I think this one was tough for me because she had to stop, but I still had some hope in the chest. For many, stopping becomes the best option because multiple attempts have given me information saying that it really may not be worth continuing. Few eggs, very poor embryo quality, advanced age etc. When younger women have to throw it in, I can at least feel that with time their situation will change, and although it looks like the end now, they may get another shot later on. It’s also easier when the best option is donor egg, and donor egg is agreeable and affordable to the patient.

Now every doctor does get very disappointed every time a patient has a negative pregnancy test. But the story about Shari just left me hanging a little more than usual. Many eggs, nice embryos, and my sense that if she could just do more cycles her time would come. Maybe. The thing was, I couldn’t tell her it would happen, and that always makes it tough. And I couldn’t lay on the optimism thing, even though had some. After 4 cycles, the energy and drive to continue has to come from the patient.

But I will continue to have hope for her. Maybe she will fall into an insurance program that will get her at least one more cycle. She doesn’t have much time for that. May be her financial situation will change and she will get to donor egg. This she has a little time for. And maybe, she will get pregnant on her own, which is not out of the realm of possibilities.

Thanks for reading, and Shari is a substitute name.

Dr. Licciardi